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RESEARCH ARTICLE

3D-bioprinted Recombination Structure of Hertwig’s

Epithelial Root Sheath Cells and Dental Papilla Cells

for Alveolar Bone Regeneration

Huilin Tang 1,2,3 , Fei Bi 1,2,3 , Guoqing Chen , Shuning Zhang 1,2,3 , Yibing Huang 1,2,3 , Jiahao Chen 1,2,3 ,
4
Li Xie , Xiangchen Qiao , Weihua Guo 1,2,3 *
5,6
7
1 State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China
2 National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
3 Department of Pediatric Dentistry, West China School of Stomatology, Sichuan University, Chengdu, China
4 Department of Human Anatomy, School of Medicine, University of Electronic Science and Technology of China,
Chengdu, China
5 National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan
University, Chengdu, China
6 Engineering Research Center of Oral Translational Medicine, Ministry of Education, State Key Laboratory of Oral Diseases,
National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
7 Chengdu Renjitiancheng Biotechnology Limited Corporation, Chengdu, China

Abstract: Three-dimensional (3D) bioprinting is an emerging method for tissue regeneration. However, promoting the
epithelial-mesenchymal interaction (EMI), while maintaining the characteristics of epithelial cells has always been a challenge
in tissue engineering. Since EMI acts as a critical factor in bone regeneration, this study aims to promote EMI by recombining
epithelial and mesenchymal cells through 3D bioprinting. Hertwig’s epithelial root sheath (HERS) is a transient structure
appeared in the process of tooth root formation. Its epithelial characteristics are easy to attenuate under appropriate culture
environment. We recombined HERS cells and dental papilla cells (DPCs) through 3D bioprinting to simulate the micro-
environment of cell-cell interaction in vivo. HERS cells and DPCs were mixed with gelatin methacrylate (GelMA) separately
to prepare bio-inks for bioprinting. The cells/GelMA constructs were transplanted into the alveolar socket of Sprague-Dawley
rats and then observed for 8 weeks. Hematoxylin and eosin staining, Masson staining, and immunohistochemical analysis
showed that dimensional cultural pattern provided ideal environment for HERS cells and DPCs to generate mineralization
texture and promote alveolar bone regeneration through their interactions. 3D bioprinting technology provides a new way for
the co-culture of HERS cells and DPCs and this study is inspiring for future research on EMI model.
Keywords: Epithelial-mesenchymal interaction; 3D bioprinting; Hertwig’s epithelial root sheath cell; Alveolar bone
regeneration

*Correspondence to: Weihua Guo, Department of Pedodontics, West China College of Stomatology, Sichuan University, No.14, 3 Section,
rd
Renmin South Road, Chengdu 610041, PR China; guoweihua943019@163.com
Received: February 1, 2022; Accepted: April 20, 2022; Published Online: June 10, 2022
(This article belongs to the Special Issue: 3D Bioprinting with Photocurable Bioinks)

Citation: Tang H, Bi F, Chen G, et al., 2022, 3D-bioprinted Recombination Structure of Hertwig’s Epithelial Root Sheath Cells and Dental
Papilla Cells for Alveolar Bone Regeneration. Int J Bioprint, 8(3):512. http://doi.org/10.18063/ijb.v8i3.512

1. Introduction cells . Strategies to accomplish tooth regeneration by
[1]
The development of tooth is a complicated process during tissue engineering have always been an academic focus
which the epithelial cells interact with the mesenchymal in recent years [2-4] . Researchers have successfully isolated

© 2022 Author(s). This is an Open-Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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